93 research outputs found
Does gene dosage really matter?
Mechanisms to compensate for dosage differences of genes on sex chromosomes are widespread in animals and have been thought to be critical for viability. However, in birds, compensation is inefficient, implying that for many genes dosage compensation is not critical, and for some genes, dosage differences have even been selected for
Dosage Regulation of the Active X Chromosome in Human Triploid Cells
In mammals, dosage compensation is achieved by doubling expression of X-linked genes in both sexes, together with X inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequenceβbased and/or epigenetic mechanisms that double the X output potentially in response to autosomal factor(s). To determine whether X expression is adjusted depending on ploidy, we used expression arrays to compare X-linked and autosomal gene expression in human triploid cells. While the average X:autosome expression ratio was about 1 in normal diploid cells, this ratio was lower (0.81β0.84) in triploid cells with one active X and higher (1.32β1.4) in triploid cells with two active X's. Thus, overall X-linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypes associated with triploidy. Absolute autosomal expression levels per gene copy were similar in triploid versus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with two active X's our data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expression is adjusted upward presumably by an epigenetic mechanism that senses the ratio between the number of active X chromosomes and autosomal sets. Such a mechanism may act on a subset of genes whose expression dosage in relation to autosomal expression may be critical. Indeed, we found that there was a range of individual X-linked gene expression in relation to ploidy and that a small subset (βΌ7%) of genes had expression levels apparently proportional to the number of autosomal sets
Genomic Responses to Abnormal Gene Dosage: The X Chromosome Improved on a Common Strategy
This new primer, which discusses a study by Zhang et al., provides an overview of the process by which chromosomes achieve dose compensation and the mechanisms underlying this phenomenon in Drosophila S2 cells
Sex-Specific Expression of the X-Linked Histone Demethylase Gene Jarid1c in Brain
Jarid1c, an X-linked gene coding for a histone demethylase, plays an important role in brain development and function. Notably, JARID1C mutations cause mental retardation and increased aggression in humans. These phenotypes are consistent with the expression patterns we have identified in mouse brain where Jarid1c mRNA was detected in hippocampus, hypothalamus, and cerebellum. Jarid1c expression and associated active histone marks at its 5β²end are high in P19 neurons, indicating that JARID1C demethylase plays an important role in differentiated neuronal cells. We found that XX mice expressed Jarid1c more highly than XY mice, independent of their gonadal types (testes versus ovaries). This increased expression in XX mice is consistent with Jarid1c escape from X inactivation and is not compensated by expression from the Y-linked paralogue Jarid1d, which is expressed at a very low level compared to the X paralogue in P19 cells. Our observations suggest that sex-specific expression of Jarid1c may contribute to sex differences in brain function
Post-primary education in West Ham, 1918-39.
This thesis is concerned with post-primary education in West Ham 1918-39, with
particular reference to secondary education. The realities of local educational
experience are set against a background of educational acts an economies. The
economic difficulties of the 1920s and the Depression of the 1930s were keenly felt
in West Ham despite the efforts of the predominantly Labour council to mitigate
poverty. A gap sometimes existed between the educational opportunities Labour
councillors wished to provide and those they were able to provide. Generally a
pragmatic approach was taken and certainly a secondary education was not seen as
essential for all.
Chapter One outlines West Ham's pre-1918 history and growth with reference to
local politics and immigrant and religious groupings. West Ham's interwar history
is told in greater detail. Chapter Two relates the difficulties encountered by the
West Ham Education Committee in its decision to establish compulsory
continuation schools, not least from the parents of West Ham. West Ham was one
of the few areas in the country which succeeded in implementing compulsory
continuation education albeit for a limited period. A section on technical education
is also included in this chapter, although detailed treatment is hampered by a
scarcity of records.
Chapter Three examines West Ham's secondary school scholarships in the context
of the national situation. West Ham's higher elementary/central school scholarships
are subjected to the same scrutiny. Each of West Ham's secondary schools shared
a broadly similar curriculum and ethos. Chapter Four highlights these similarities
but also points out differences. Of the five interwar secondary schools, two
catered for girls, one for boys and two were mixed. Two of the secondary schools
were Catholic institutions, although both accepted non-Catholic pupils. Three of
the schools were aided and two municipal. A section is included on West Ham's
higher elementary/central schools but records are less full than those for the secondary schools. Chapter Five compares and contrasts West Ham's interwar
secondary school system with that in East Ham, its sister borough. Chapter Six
discusses both the economic and cultural factors underlying local attitudes to
post-compulsory schooling. The main conclusions drawn relate to these attitudes
which militated against any easy acceptance of such education as necessarily
beneficial
Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster
Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed βOhnoβs hypothesisβ). Although this hypothesis is well supported by expression analyses of individual X-linked genes and by microarray-based transcriptome analyses, it was challenged by a recent study using RNA sequencing and proteomics. We obtained new, independent RNA-seq data, measured RNA polymerase distribution and reanalyzed published expression data in mammals, C. elegans and Drosophila. Our analyses, which take into account the skewed gene content of the X chromosome, support the hypothesis of upregulation of expressed X-linked genes to balance expression of the genome
Loss of Maternal CTCF Is Associated with Peri-Implantation Lethality of Ctcf Null Embryos
CTCF is a highly conserved, multifunctional zinc finger protein involved in critical aspects of gene regulation including transcription regulation, chromatin insulation, genomic imprinting, X-chromosome inactivation, and higher order chromatin organization. Such multifunctional properties of CTCF suggest an essential role in development. Indeed, a previous report on maternal depletion of CTCF suggested that CTCF is essential for pre-implantation development. To distinguish between the effects of maternal and zygotic expression of CTCF, we studied pre-implantation development in mice harboring a complete loss of function Ctcf knockout allele. Although we demonstrated that homozygous deletion of Ctcf is early embryonically lethal, in contrast to previous observations, we showed that the Ctcf nullizygous embryos developed up to the blastocyst stage (E3.5) followed by peri-implantation lethality (E4.5βE5.5). Moreover, one-cell stage Ctcf nullizygous embryos cultured ex vivo developed to the 16β32 cell stage with no obvious abnormalities. Using a single embryo assay that allowed both genotype and mRNA expression analyses of the same embryo, we demonstrated that pre-implantation development of the Ctcf nullizygous embryos was associated with the retention of the maternal wild type Ctcf mRNA. Loss of this stable maternal transcript was temporally associated with loss of CTCF protein expression, apoptosis of the developing embryo, and failure to further develop an inner cell mass and trophoectoderm ex vivo. This indicates that CTCF expression is critical to early embryogenesis and loss of its expression rapidly leads to apoptosis at a very early developmental stage. This is the first study documenting the presence of the stable maternal Ctcf transcript in the blastocyst stage embryos. Furthermore, in the presence of maternal CTCF, zygotic CTCF expression does not seem to be required for pre-implantation development
Stabilization and Localization of Xist RNA are Controlled by Separate Mechanisms and are Not Sufficient for X Inactivation
- β¦